Recent meta-analyses suggest that once-daily dihydropyridines and angiotensin-converting enzyme inhibitors cause similar decreases in left ventricular (LV) mass for comparable decreases in blood pressure (BP). However, some dihydropyridines, such as felodipine-extended release (ER), still increase sympathetic activity and may, therefore, be less effective in decreasing LV mass. To evaluate the effects of long term antihypertensive treatment with nifedipine-gastrointestinal therapeutic system (GITS) and felodipine-ER compared with enalapril on LV mass relative to the extent of BP control (assessed by 24 h ambulatory BP monitoring) and sympathetic activity (assessed by plasma catecholamine concentrations). Enalapril was started at 10 mg/day, felodipine-ER at 5 mg/day and nifedipine-GITS at 30 mg/day, all once daily. Doses were increased to 20 mg/day, 10 mg/day or 60 mg/day, respectively, if the office BP remained 160/90 mmHg or greater at the end of the dosing interval. Evaluable echocardiograms were obtained for 116 patients at the end of the study (30 weeks of treatment). On 24 h ambulatory BP monitoring, nifedipine-GITS caused a consistent decrease in BP throughout the 24 h dosing interval, whereas felodipine-ER caused a more marked fall in BP during the day, and enalapril's effects diminished during the night and had disappeared by the morning. Only felodipine-ER significantly increased supine and standing plasma noradrenaline by more than 50% similarly after six, 18, and 30 weeks of treatment. In BP responders (decrease in systolic BP 10 mmHg or greater), enalapril and nifedipine-GITS caused clear decreases in LV mass by 12 to 16 g/m2, whereas felodipine-ER was less effective (decrease by only 6 g/m2, P<0.01 versus enalapril). Once-daily dihydropyridines should not be regarded as one homogeneous class and, compared with felodipine-ER, nifedipine-GITS exhibits a better profile regarding 24 h BP control, sympathetic activation and regression of LV mass.